A form of amyloidosis occuring in a variety of chronic inflammatory diseases is caused by the deposition in tissues of a fibrillar protein called amyloid A (AA). An "acute phase" serum protein that is chemically and immunochemically related to AA has been identified. This serum amyloid A (SAA) protein is transported as a high density lipoprotein (HDL). We have isolated SAA in quantity from HDL and demonstrated at least six polymorphic forms of the protein that share common antigenic sites but differ in electrophoretic mobility and amino acid composition. We propose to define the nature of the microheterogeneity of SAA and determine the primary structure of the major form(s) of SAA, thereby characterizing the large COOH-terminal peptide common to SAA and absent from AA. We plan to characterize the nature of SAA-enriched HDL, to determine the capacity of SAA to form independent lipoprotein complexes in vivo, and to define the apolipoprotein properties of SAA using immunoadsorption chromatography, ultracentrifugation, electron microscopy, fluorescence depolarization and other optical methods, and gel filtration. A radioimmunoassay specific for SAA will be developed, validated, and used to study the putative conversion of SAA to AA and to quantify SAA levels in a variety of normal and abnormal states. Finally, the possibility that the polymorphic forms of SAA are related as precursors and products will be investigated.